Department of Systems Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17456-61. doi: 10.1073/pnas.1114210108. Epub 2011 Oct 10.
Although the importance of the cellular microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the microenvironment on tumor cell behavior.
尽管细胞微环境（土壤）在癌细胞的侵袭和转移中具有重要作用已经得到了广泛认可，但技术挑战限制了评估微环境对癌细胞分子水平影响的能力。在这里，我们展示了一种实验策略，即微阵列实验的竞争异种杂交，可以通过当人癌细胞异种移植到免疫缺陷小鼠的不同器官部位时，独立提取癌细胞和宿主细胞的基因表达数据，来描述不同微环境对癌细胞的影响。令人惊讶的是，基因表达数据分析表明，脑微环境诱导转移癌细胞的完全重编程，导致获得神经元细胞特征，并模拟发育过程中的神经发生。我们还表明，表观遗传变化与癌细胞中转录重编程同时发生。这些观察结果为竞争异种杂交微阵列实验提供了原理证明，以描述微环境对肿瘤细胞行为的影响。
